Treatment with prostaglandin F2 alpha (PGF2 alpha) was evaluated in 21 queens with open-cervix pyometra. The PGF2 alpha was administered (0.1 or 0.25 mg/kg of body weight, sc, q 12 to 24 h) for 3 or 5 days. Transient postinjection reactions caused by PGF2 alpha administration included vocalization, panting, restlessness, grooming, tenesmus, salivation, diarrhea, kneading, mydriasis, emesis, urination, and lordosis. Reactions began as quickly as 30 seconds after PGF2 alpha administration and lasted as long as 60 minutes. All queens improved clinically after PGF2 alpha treatment. One month after completion of the initial series, 1 queen required a second series of PGF2 alpha injections before pyometra resolved. Of 21 queens, 20 (95%) resumed normal estrous cycles without further treatment and 17 (81%) delivered normal litter(s). Use of PGF2 alpha is an acceptable treatment for open-cervix pyometra in queens.