Treatment with the serotonin (5-HT) reuptake inhibitor Zimelidine, 20 mg/kg/24 hrs, s.c., for 14 days increased the duration of vaginal cycles in 3 month-old Long Evans hooded rats. It induced persistent vaginal estrus in 12 or 16 ten-month old animals, and blocked reinitiation of vaginal cycles by L-dopa in 10 of 10 twenty-month old rats. A single injection of zimelidine at 1400 h did not alter the vaginal smear pattern of young or middle-aged cyling females or old constant estrus females. Also, a single dose of zimelidine at 1400 h on the day of vaginal proestrus had no effect on serum LH values in young females. The serotonergic neurotoxin 5,7-hydroxytryptamine, 4 microgram, injected into the ventral and dorsal raphe areas (after desipramine, 25 mg/kg i.p.) reinitiated vaginal cycling in 8 of 13 twenty-month old rats.