Rats received lateral intracerebroventricular (icv) injection of sulfated or desulfated cholecystokinin octapeptide (CCK-8-S or CCK-8-D, respectively) and subsequent grooming behaviors were observed using a behavioral sampling technique. CCK-8-S (2.0 to 4.0 micrograms in 10 microliter) elicited a significant increase in grooming behaviors relative to the controls, but the relatively inactive CCK-8-D did not. Excessive grooming induced by CCK-8-S produced less grooming than did the adrenocorticotropic hormone fragment, ACTH1-24 (1.0 microgram in 10 microliter). An icv injection of CCK-8-S 3 h before the icv injection of ACTH1-24 inhibited the usual excessive grooming produced by the ACTH. Conversely, prior injection of ACTH1-24 abolished the increased grooming induced by CCK-8-S. Thus, the sulfated cholecystokinin octapeptide and ACTH1-24 exhibited short-term cross tolerance for excessive grooming. These results suggest that the colocalization of corticotropin releasing hormone and CCK-8 in neurons may have functional significance in connection with stress-related neuronal systems.