The discovery that many cells express vitamin D receptors and the recognition of widespread vitamin D insufficiency has stimulated interest in the potentially beneficial effects of vitamin D in nonskeletal conditions. The disorders in which vitamin D may play a role include cancer, infection, cardiovascular disease, schizophrenia, and immune-mediated diseases such as multiple sclerosis, insulin-dependent diabetes, and asthma (1–3). Vitamin D has potent immunomodulatory properties, acting on cells of the innate immune system to inhibit proinflammatory cytokine production and induce antimicrobial peptide synthesis (4). It inhibits adaptive Th1 responses (4), but has variable effects on human Th2 responses. Vitamin D inhibits cord blood interferong, interleukin (IL)-4, and IL-13 responses (5), but enhances allergen-specific Th2 responses in cultures of adult peripheral blood cells (6). In contrast, a recent study demonstrated dosedependent inhibition of both Th1 and Th2 responses, except at the highest concentration tested, where less suppression, but no enhancement of either Th1 or Th2 responses, was observed (7). In the same cultures, the antiinflammatory cytokine IL-10 was induced in a dose-dependent manner, except at this high concentration. Vitamin D also restores the impaired steroid-induced IL-10 response observed in patients with steroid-refractory asthma (8). Vitamin D has been shown to promote a tolerogenic phenotype in human dendritic cells, leading to the induction of Foxp31 regulatory T cells (Treg)(9). Together these data suggest dose-dependent effects of vitamin D on immune responses, with all but the highest concentrations being antiinflammatory and promoting IL-101 and Foxp31 Treg populations. In this issue of the Journal, Brehm and colleagues (pp. 765–771) describe the serum vitamin D status of 616 Costa Rican children with asthma aged 6 to 14 years (10). They report that 3.4% were deficient, 28% were insufficient, and that vitamin D levels were inversely associated with markers of asthma and allergy severity. Low vitamin D levels were associated with elevated total IgE and eosinophil counts, and increased the likelihood of methacholine airway responsiveness, asthmarelated hospitalization, and use of antiinflammatory medication. Without dietary supplementation, humans obtain about 90% of their vitamin D from sunlight exposure and 10% from diet. The prevalence of vitamin D deficiency/insufficiency in children with asthma living in Costa Rica is consistent with other studies reporting widespread vitamin D insufficiency even in areas with abundant sunshine (11). The increasing tendency to stay indoors and the promotion of sunshine avoidance to prevent skin cancer by covering up and sunblock are the most likely reasons for inadequate vitamin D status. It is difficult to compensate for declining sunlight-derived vitamin D by dietary means alone because vitamin D is naturally present in very few foods (oily fish, fish liver oil, egg yolk), although in some countries margarine and/or milk are fortified. Although Brehm and coworkers (10) considered 25-hydroxyvitamin D (25 [OH] D) levels less than 20 ng/ml to be deficient and less than 30 ng/ml to be insufficient, controversy surrounds these cutoffs (1). In the United Kingdom, 10 ng/ml 25 (OH) D has been the traditional cutoff for vitamin D deficiency, since rickets and osteomalacia are associated with 25 (OH) D values less than or equal to 8 ng/ml. However, cutoffs of 15 ng/ml for ‘‘hypovitaminosis D’’and 20 to 30 ng/ml and higher have been advocated with much debate about the inverse relationship with parathyroid hormone in defining the cutoffs (1). Since some individuals have …