Sex differences in the mutagenic activation of dimethylnitrosamine (62759) (DMN) were studied. Male and female CD-mice and CD-rats were injected with conidia of tester strain H59 or N23 of Neurospora- crassa immediately before intramuscular injections of 100 milligrams per kilogram of DMN. Conidia were recovered from liver, lung, and kidney 16 hours after DMN treatment. The adenine-3 forward mutation frequency was determined for H59 and the induction of reverse mutations was determined for N23. In-vitro induction of forward and reverse mutations was determined using mouse and rat S9 organ homogenates. DMN was activated to mutagenic metabolites by the liver, lung, and kidney of female and male mice in host mediated assay tests. In-vivo mutation frequency was greatest for the liver and was about the same in male and female mice. Mutation frequency by the kidney was much higher in male than female mice. Number of mutants in mouse in-vitro tests was highest with S9 from the lung and lowest in liver S9. No sex differences occurred for mice in- vitro activation systems. Results from rat in-vivo and in-vitro tests were similar to those for mice, except that no sex difference occurred for rat kidney in-vivo DMN activation. The authors conclude that further study is needed to determine the reasons for the difference in DMN in-vivo and in-vitro activation by mouse kidney in the Neurospora assay system.