Using several routine screening procedures to determine anti-depressant drug activity in experimental laboratory animals, ketamine HCl was found to possess significant activity over a wide-range of oral doses. The tests used were (a) reversal of tetrabenazine-induced ptosis in mice, (b) reversal of reserpine-induced hypothermia in rats, (c) enhancement of yohimbine toxicity in mice and (d) inhibition of oxotremorine-induced tremors in mice. In general, the anti-depressant potency of ketamine HCl was substantially less than that of imipramine HCl.