The Nb2 rat lymphoma PRL bioassay and standard RIA techniques were used to compare the impact of aging on immunoreactive (ir) and bioactive (bio) plasma PRL levels in 3- to 5- and 22- to 24-month-old male Copenhagen-Fischer rats. Basal plasma irPRL levels were significantly higher, while bioPRL were significantly lower in old compared to young rats. Administration of 10 mg/kg morphine similarly increased plasma irPRL levels in both age groups, but elevations in bioPRL were significantly lower in the older animals. Administration of 1 mg/kg haloperidol significantly increased circulating levels of ir- and bioPRL in both age groups, but these responses were significantly attenuated in the older rats. Treatment with 10 mg/kg bromocryptine resulted in significantly greater decreases in plasma irPRL levels in young rats, but induced similar decreases in bioPRL levels in both age groups. Administration of 25 micrograms/kg TRH induced similar increases in both ir- and bioPRL levels in young and old male rats. These results demonstrate that basal plasma bioPRL levels are significantly lower in old compared to young male rats, and specific drug treatments differentially alter the ratio of plasma bio- vs. irPRL levels in these age groups. These findings suggest that during the aging process not only quantitative changes but also qualitative changes occur in PRL secretion, which result in an overall decline in the biopotency of PRL released into the circulation.