Sixteen domestic cats were used to investigate the pituitary-adrenal, pituitary-gonadal and behavioral consequences of an unpredictable handling and husbandry routine. After a 10-day baseline period of standard laboratory procedures, eight cats ('stressed cats', STR) were subjected to a 21-day period of altered caretaking characterized by irregular feeding and cleaning times, absence of talking and petting by humans, and daily unpredictable manipulations. Eight control cats (CON group) were maintained for 21 days on the standard caretaking schedule. Behavior was recorded on time-lapse video 24 h day-1, urine was collected daily for cortisol analyses, and hormone stimulation tests with synthetic adrenocorticotropic hormone (ACTH) and luteinizing hormone-releasing hormone (LHRH) were conducted before and after the 3-week treatment period. Results indicate that the STR cats were chronically stressed by the altered caretaking routine. Urinary cortisol concentrations were consistently elevated throughout the 3-week period, adrenal sensitivity to ACTH was enhanced and pituitary sensitivity to LHRH was reduced. Active exploratory and play behavior was suppressed, and STR cats spent more time awake/alert and attempting to hide. Hiding was negatively correlated with cortisol concentration and, therefore, may be an important behavior for coping with uncontrollable and unpredictable captive environments. These results indicate that qualitatively poor caretaking is a potent psychological stressor for confined cats that may eventually compromise reproduction through behavioral or physiological mechanisms. To promote well-being, caged cats should be provided with appropriate places for concealment.