Sunscreens absorb solar radiation and block the cutaneous synthesis of vitamin D3. Because of this property, we tested sunscreens as a research tool for photodependent reactions. The concept was evaluated by determining the segmental body contributions to vitamin D3 production. Twenty-seven healthy, untanned white persons with skin type III applied a sunscreening agent to selected body areas (head and neck, arms, trunk, or legs) to block UVB absorption. Control groups comprised subjects who either covered the whole body with, or did not apply, sunscreen. Serum vitamin D3 was determined 1 hour before and 24 hours after exposure to a suberythemic dose of UVB light (27 millijoule/cm2). Basal vitamin D3 levels were similar among the different groups (mean +/- standard error for the entire population: 2.8 +/- 0.7 ng/ml). Segmental contribution to the UVB-stimulated cutaneous synthesis of vitamin D3 appeared to be largely a function of surface area. Serum vitamin D3 increased significantly (p less than 0.05) in subjects exposing the trunk (13.7 +/- 3.2 ng/ml), legs (11.2 +/- 3.2 ng/ml), and entire body (12.6 +/- 2.8 ng/ml). In subjects exposing the head and neck or arms, the post-UVB vitamin D3 level was higher than the basal level (5.8 +/- 4.0 and 4.5 +/- 2.2 ng/ml), but the difference was not significant (p greater than 0.5). Whole body application of sunscreen completely blocks the vitamin D3 response to UVB. We conclude that short-term (single) application of sunscreens may be used as a simple complementary technique for the evaluation of photodependent reactions in physiologic and pathologic conditions.