A total of 24 patients presenting with small-cell lung cancer either resistant to or relapsing within 3 months after first-line treatment were entered in a phase II study of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU). ACNU was given i.v. at a dose of 75 mg/m2 every 6 weeks. We observed a partial response of 7 months' duration in one patient and one case of stable disease that lasted for 6 months; all other subjects exhibited progressive disease. Two patients developed brain metastases during treatment. The toxicity of ACNU consisted mainly of bone marrow suppression, especially thrombocytopenia. At this dose and on this schedule, ACNU shows minimal activity as second-line treatment in small-cell lung cancer.