To determine the association between leprosy and HTLV-I, 450 and 394 leprosy patients in two sanatoriums in Japan (Sanatorium-A in Okayama prefecture and Sanatorium-B in Gunma prefecture) were investigated serologically for antibodies to HTLV-I. Serology was positive for HTLV-I in 38 (8.4%) of 450 leprosy patients in Sanatorium-A and in 34 (8.6%) of 394 patients in Sanatorium-B. Prevalence was much higher than that in the general population of these areas in Japan. A large proportion of HTLV-I-positive patients in both sanatoriums came from HTLV-I nonendemic areas in Japan, suggesting that HTLV-I infection occurred after the patients arrived at the sanatoriums. Infection through sexual contact or reuse of needles for frequent vaccination are possible routes of infection for HTLV-I in these cases.