The effect of chronic daily orogastric gavage with water (5 mL/kg) on behavior and physiology was evaluated in male Sprague-Dawley rats. Treatment groups included: unmanipulated control, restraint control, dry gavage, and gavage, with all rats singly housed (n = 9 or 10 per group). In addition, a group of pair-housed rats (n = 18) was included to determine whether social housing affected response to gavage. Weekly body weights and food consumption were recorded as well as use of a nylon chew toy for enrichment. Feces were collected biweekly at the end of the light and dark phases for fecal corticoid metabolite determinations. After 28 d of treatment, animals underwent conditioned place preference testing to evaluate sensitivity to motivational properties of the anxiolytic drug chlordiazepoxide (5.6 mg/kg SC). Brain and paired adrenal gland weights were collected at necropsy. Week 2 total fecal corticosterone levels were elevated in all groups and attributed to a fire alarm accidentally tripped during building renovations. No differences occurred in body weight or food consumption between any groups. All groups used a nylon chew toy given for enrichment and demonstrated mild preference for the drug-associated chamber. Fecal weights and corticoid metabolite levels were similar between all groups at week 4 and showed normal diurnal variation. No biologically significant variations were noted in brain or paired adrenal gland to body weight ratios. We conclude that orogastric gavage of aqueous solutions at 5 mL/kg does not negatively affect the welfare of laboratory rats acclimated to handling.