PURPOSE: The highest incidence of urinary tract infection in females occurs in elderly women. This study was done to determine whether this is due to the declining immune response that occurs during advancing age, or the menopausal state in the aged. MATERIALS AND METHODS: Adult female monkeys (average age 19 years) were studied, half being subjected to bilateral oophorectomy to produce the menopause. In addition, old females (average age 29 years) already at menopause were studied before and after hormonal replacement with estradiol and progesterone. Bacterial adherence to vaginal cells was studied prior to and after urethral infection with E. coli. Plasma estradiol and progesterone levels were done, as well as white blood counts, plasma cytokine assays and serum antibody titers. RESULTS: Bacteriuria was not prolonged, nor was there a significant difference in bacterial adherence to vaginal cells due to menopause. Interleukin-1 levels were depressed after surgical menopause but not as much as found in the old menopausal females and this low level was not corrected by hormonal replacement. The initial interleukin-2 levels were higher after spontaneous menopause, but the increasing plasma levels seen in cycling animals after infection did not occur in the aged menopausal females following infection even after hormone replacement. The antibody titers to the E. coli infection showed a trend to a lessened response to infection after menopause but were not significantly decreased. CONCLUSIONS: The deficient Il-1, Il-2 and antibody response following infection was not corrected by hormone replacement and thus appears to be due to aging rather than lack of female hormones. These facts may be explained by the T cell senescence known to occur in aged individuals.