We estimated the risk of second cancers among 1507 patients with Hodgkin's disease treated at Stanford University Medical Center since 1968. Eight-three second cancers occurred more than one year after diagnosis, as compared with 15.9 expected on the basis of rates in the general population (relative risk, 5.2; 95 percent confidence interval, 4.2 to 6.5). The mean (+/- SE) 15-year actuarial risk of all second cancers was 17.6 +/- 3.1 percent, of which 13.2 +/- 3.1 percent was due to solid tumors. The risk of leukemia appeared to reach a plateau level of 3.3 +/- 0.6 percent at 10 years, whereas non-Hodgkin's lymphoma continued to increase, to 1.6 +/- 0.7 percent by the end of the follow-up period. The risk of solid tumors did not vary significantly according to treatment category, with the array of neoplasms resembling that previously observed in populations exposed to radiation and in immunosuppressed groups. The risk of leukemia, although elevated after radiation therapy alone (relative risk, 11; 95 percent confidence interval, 1.2 to 38), was much higher after either adjuvant chemotherapy (relative risk, 117; 95 percent confidence interval, 69 to 185) or chemotherapy alone (relative risk, 130; 95 percent confidence interval, 26 to 380). These data suggest that the risk of solid tumors after therapy for Hodgkin's disease continues to increase with time.