Synthesis of vitamin D3 is determined primarily by cutaneous exposure to UV light irradiation (UVR). We studied the effect of exogenous 1,25-dihydroxyvitamin D on the cutaneous synthesis of vitamin D. Eight normal subjects, all caucasian, were randomly assigned to receive 1,25-dihydroxyvitamin D (0.5 micrograms daily) or no treatment for 20 days, followed 30 days later by the other treatment for 20 days. After 5 days, each experimental group (untreated and calcitriol treated) was exposed to one minimal erythema dose of UVR (UVR amplification test). Serum vitamin D3 concentrations reached peak levels 24 h after UVR exposure, and the mean values in the untreated and calcitriol-treated subjects were similar: 13.5 +/- 0.6 (+/- SD) ng/mL (35.1 +/- 1.5 nmol/L) and 13.0 +/- 0.6 ng/mL (33.8 +/- 1.5 nmol/L), respectively (P greater than 0.1). An identical 24-h post-UVR serum vitamin D3 value [13.5 ng/mL (35.0 nmol/L)] was found in a hypoparathyroid patient taking calcitriol (1 microgram daily). Thus, the cutaneous synthesis of vitamin D3 in response to acute UVR exposure was not inhibited by the administration of 1,25-dihydroxyvitamin D orally.