Abnormal reward-seeking behavior is a key feature in several psychiatric and neuroscience diseases. Though there are numerous paradigms for measuring reward-seeking behavior in rodents, each has limitations that affect the ability of the researcher to make conclusions on the reward-seeking behavior per se. Here, we describe a novel approach for monitoring reward-seeking behavior in rodents: the female urine-sniffing test (FUST). Lately, we found that sniffing of estrus female urine by male mice is a preferred activity of numerous mice strains and rats. In addition, this preferred activity was found to be accompanied by biological changes linked to hedonic and rewarding activities. The FUST was also been found to be sensitive to behavioral and genetic manipulation and to drug treatment related to depression and mania.