The liver cells of male and female wild mice (Peromyscus leucopus and Mus musculus) have been studied in young, adult, and old age groups. Because P. leucopus displays a life expectancy of 7-8 years, the age groups of this strain were from 5.5 to 68 months. M. musculus survives only to about 2.5 years; therefore, the age groups of this strain ranged from 6 to 27 months. Protein lateral diffusion in hepatocyte membranes was measured by means of fluorescence recovery after photobleaching (FRAP) in liver smears. The peroxide-induced autofluorescence was utilized as a fluorescent label, which in H2O2 treated liver smears is caused by the oxidation of riboflavin bound uniformly to all proteins of the cell membrane. This way the average lateral diffusion constant (D) and the fractional recovery of those proteins can be measured. In both males and females of both strains D displayed a negative linear age correlation. Intraspecies sex differences were small and statistically insignificant. However, interspecies comparisons of males or females resulted in a strongly significant difference: although the intercept points of the regression lines describing D were identical in both strains (3.1 x 10(-10) cm2/sec), the decay of D with aging was about 2.5 times faster in the short-living M. musculus than in the long-living P. leucopus. By the end of life expectancy, both strains reached practically identical values (about 1.9 x 10(-10) cm2/sec). The results lend further support to the membrane hypothesis of aging.