One hundred fifty-one patients who were positive for antibody to human immunodeficiency virus (HIV) and intolerant of zidovudine received oral didanosine at a dose adjusted by weight to a maximum of 12.5 mg/(kg.d). After 1 year of follow-up, 49 patients were still receiving didanosine; 19 had died during therapy and 23 thereafter. Therapy had been discontinued in 10 cases because of continued deterioration in health and in the remainder because of adverse reactions. Only 11 of 38 patients with positive results in an ELISA for p24 antigen before therapy had a significant reduction in titer. CD4 lymphocyte subset counts were more likely to rise for patients who had only constitutional disease due to HIV than for those with AIDS. Eleven percent of treated patients gained > 2.5 kg. Diarrhea was the commonest side effect, occurring in 60% of cases. Pancreatitis developed in six cases (with two deaths) and asymptomatic hyperamylasemia in 13. Seven patients developed glucose tolerance in the diabetic range. Peripheral neuropathy was documented in 12 instances but was reversible on cessation of therapy in six.