In addition to age-related deficits in morphine antinociception in female rats, gender and gonadectomy differences have also been observed, with male rats displaying greater magnitudes of effects than females and castrated males. Since there are little data indicating how aging, gender, and gonadectomy interact in modulating morphine antinociception, the present study evaluated alterations in this response as functions of age (6, 12, 18, and 24 months), gender, and gonadal status (intact, gonadectomized) across a dose range (1-10 mg/kg) and time course (0.5-2 h) on the tail-flick test. The maximal percentage effect (MPE) of morphine (1 mg/kg) was significantly increased in castrated males (18 months), sham females (18 and 24 months), and ovariectomized females (18 months) relative to 6-month-old groups. Increases in the MPE of morphine (1 mg/kg) occurred in sham females (24 months) relative to corresponding sham males and ovariectomized females. The MPE of morphine (2.5 mg/kg) was significantly increased in sham males (18 months) and decreased in sham females (12 months). Decreases in the MPE of morphine (2.5 mg/kg) occurred in castrated males (18 and 24 months) as well as sham (18 months) and ovariectomized (18 and 24 months) females relative to sham males. Whereas the MPE of morphine (5 mg/kg) was unchanged by these variables, the MPE of morphine (10 mg/kg) was significantly decreased in sham females (18 and 24 months) relative to females aged 6 months, as well as males and ovariectomized females aged 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)