Twenty institutions/cooperative groups tabulated second cancers among 12,411 patients diagnosed with Hodgkin's disease between 1960 and 1987, giving 82,850 person-years of observation. Overall, 631 second cancers were observed, as compared with 223.25 expected (observed (O) to expected (E) ratio 2.83, p < 0.001) at least one year after the diagnosis of Hodgkin's disease. Second cancers were acute leukaemias (AL) in 158 cases as compared with 5.75 expected (O/E = 27.48, p < 0.001), non-Hodgkin's lymphomas (NHL) in 106 cases as compared with 3.34 expected (O/E = 31.77, p < 0.001), and solid tumors (ST) in 367 cases as compared with 214.16 expected (O/E = 1.71, p < 0.001), with no differences between males and females. Excess of ST was observed for the following anatomic sites: salivary gland, small intestine, colon, bronchus, pleura, bone, skin other than melanoma and thyroid in males; salivary gland, bronchus, pleura, skin other than melanoma and breast in females. While the excess of second AL and NHL was significant over the 1-14 year period after the start of initial therapy, that of second ST became apparent after the fifth year, increasing with time. Overall, the 15-year cumulative incidence rate of second cancer was 11.2%. It was 2.2%, 1.8% and 7.5% for second AL, NHL and ST, respectively. While the cumulative incidence of AL and NHL plateaued after 17 years, that of ST was still increasing. To analyse whether a particular treatment category was associated with an increased risk of second cancer, a prognostic study was performed on the 11,241 patients who achieved a complete remission and were continuously disease-free. Overall, 87 patients developed an AL, 68 a NHL, and 231 a ST. Combined modality treatments including MOPP or MOPP-like chemotherapy were associated with the higher risk of second AL (Relative risk (RR) = 17.11; p < 0.001) followed by age above 50 (RR > 4.50; p < 0.001), advanced clinical stage (RR > 2.50; p < 0.001), splenectomy (RR = 1.65; p < 0.05) and MOPP or MOPP-like chemotherapy used alone (RR = 2.20; p < 0.05). Factors associated with an increased risk of second NHL were age above 30 (RR > 3.5; p < 0.001), male gender (RR = 1.82; p < 0.05) and clinical stage III (RR = 1.70; p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)