The purpose of the present study was to analyze the effect of two different beta blocking agents, metipranolol (Trimepranol) and dl-propranolol (Inderal), upon erythropoietin production, erythropoietin responsive cell compartment and erythrocyte production. The effect on erythropoietin production: in rats metipranolol or dl-propranolol was injected daily in a single dose of 10 mg/kg b.wt. On the 5th day, the rats were exposed to an atmospheric pressure of 353.7 torr (47.1 kPa, 6000 m) to stimulate erythropoietin production. The onset of hypoxic exposure was started 1, 4, 12 or 24 hr after the last injection of beta blocking drugs. After the termination of hypoxia, erythropoietin plasma levels were determined in polycythemic mice. The rats treated with metipranolol 1 and 4 hr before hypoxia produced significantly less erythropoietin in response to hypoxia than saline-treated control animals. The effect on erythropoietin responsive cell compartment: polycythemic mice were treated with metipranolol or dl-propranolol in doses of 10 to 40 mg/kg b.wt. and with an erythropoietin standard. Radioiron incorporation into red blood cells in control mice and in mice pretreated with beta blocking agents was not significantly different. The effect on erythrocyte production: in rats treated daily with metipranolol in a single dose of 10 mg/kg b.wt., for a period of 10 days, the rate of erythropoiesis measured by the incorporation of 59Fe into red blood cells was decreased, dl-propranolol (10 mg/kg b.wt.) did not reduce the rate of erythropoiesis. Our results demonstrate that the changes in erythropoiesis after administration of metipranolol may be caused by reduction of erythropoietin production with a consequent reduction of the erythrocyte production rate.