Groups of 30 adult Swiss mice of both sexes from the Eppley Institute breeding colony were treated with 37.5 or 75 mg 2-hydroxyethylnitrosourea (HENU)/l citrate buffer, given as drinking water on 4 days/week from 6-8 weeks of age for life. A third group of mice was untreated. Incidences of generalized B cell lymphoma (BCL) were 67% (males) and 87% (females) for the higher dose of the nitrosourea, 29% (males) and 79% (females) for the lower dose and 0% (males) and 7% (females) for the untreated mice. Tumor latencies were 23 weeks (high dose) and 27 weeks (low dose) in the females and 6-7 weeks longer in the males. A B-cell origin of the lymphomas was indicated by the pathology and tumor distribution and was confirmed in 4 mice by immunophenotyping and in 6 mice by probes for gene rearrangements. This system may be an effective means of inducing B cell lymphoma with a carcinogen.