The effect of the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF9-41 (alpha H CRF9-41; 25 and 50 micrograms) was examined in four strains of mice (BALB/C, NIH Swiss, CF-1, and CD) in the elevated plus-maze anxiolytic test and found to significantly increase percent open arm activity in only the BALB/C mice. A marginal anxiolytic response was obtained in NIH Swiss, while no effect of the antagonist was noted in CF-1 or CD mice in this test. Diazepam (1-4 mg/kg IP) significantly increased percent open arm activity in all four mouse strains. Thus, all strains were sensitive to the effects of a known anxiolytic in this test. The locomotor-suppressing effect of the agonist CRF was assessed in the four strains of mice. While CRF suppressed locomotor activity in each of the strains, the peptide was more efficacious and more potent in the BALB/C strain than in any of the other three strains. The behavioral differences in responsiveness to CRF and the antagonist alpha H CRF9-41 could not be explained on the basis of differential binding of CRF to forebrain membranes in the four mouse strains. These data suggest that the BALB/C mouse is more sensitive to the behavioral effects of CRF and its antagonist than other strains and may be a useful strain for examining the effects of CRF and/or stress.