Groups of 4-day cyclic rats were injected (i.p.) with LY 134046 (50 mg/kg), a central inhibitor of phenylethanolamine N-methyltransferase, or saline at 09.00, 13.00 and 19.00 h on the day of proestrus. The incidence of ovulation was examined the following estrous morning. There was no difference in the number of ova in drug-treated animals compared to saline-treated controls. In other groups of 4-day cyclic rats, LY 134046 or saline was injected daily at 10.00 h for 5 consecutive days from proestrus to proestrus inclusive. The animals were decapitated the following day and ova were counted. Epinephrine concentrations were determined by radioenzymatic assay in the mediobasal hypothaiamus (MBH) and the medial preoptic area (MPOA). All saline-treated controls and 10/14 of the drug-treated animals had ovulated, while epinephrine concentrations in the MBH and MPOA had been reduced by 95.8 and 94.7%, respectively, compared to saline-treated controls. These experiments suggest that a significant surge of luteinizing hormone occurs to initiate ovulation even after a severe reduction in central epinephrine concentration has taken place.