Due to the interest in the antidepressant potential of nonpeptide corticotropin-releasing factor (CRF)(1) receptor antagonists, the present investigation examined the antidepressant-like effects of the CRF(1) receptor antagonist CP-154,526 on the exaggerated swim test immobility in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. Chronic treatment with CP-154,526 (10 mg/kg; 2x day) for 14 days increased swimming in the Flinders Sensitive Line rats. Citalopram (5 and 10 mg/kg; 2x day) and desipramine (5 mg/kg; 1x day) also significantly increased swimming in the Flinders Sensitive Line rats, as expected. However, neither CP-154,526 nor citalopram (10 mg/kg) altered swimming times in the control Flinders Resistant Line (FRL) rats. Citalopram (10 mg/kg) and CP-154,526 also increased the abnormally low level of social interaction behavior in the Flinders Sensitive Line rats. These findings indicate that citalopram and CP154,526, a CRF(1) receptor antagonist, have both antidepressant and anxiolytic effects that can be detected in an experimental model of depression only and not in "normal" control animals.