Episodes of depression and acute psychosis in two patients receiving propranolol hydrochloride are described, and the literature on propranolol-induced depression and psychosis is reviewed. A 42-year-old woman developed severe depression, marked apathy, social withdrawal, and anorexia after taking propranolol hydrochloride (80 mg/day) for three months to control her hypertension. Five days after the dose was reduced to 40 mg/day, there was a major improvement in her depressive symptoms, with a complete resolution in eight days. Upon rechallenge with 80 mg/day of propranolol, she again experienced depressive symptoms. Atenolol 50 mg/day was substituted for the propranolol therapy, and she exhibited a complete remission of her depression. The second patient was a 63-year-old man who had been taking propranolol hydrochloride 160 mg/day for three months without incident. Because of an increased frequency of anginal attacks, the dosage was increased to 240 mg/day. Within two days, he demonstrated such agitation, excitement, and combativeness that he had to be controlled with a 25-mg dose of methotrimeprazine. When the propranolol dose was reduced to 160 mg/day, his psychotic symptoms rapidly cleared. However, when the dose was subsequently increased to 200 mg/day, he again showed increased agitation. After substituting atenolol 100 mg/day for propranolol, the patient's mental status returned to normal. Both of these patients experienced symptoms that were temporarily associated with propranolol. Both patients were subsequently controlled without symptoms with atenolol therapy. Propranolol is a highly lipophilic beta blocker that achieves high concentrations in the brain. When continued beta-blocking therapy is necessary or beta blockade is indicated, a weakly lipophilic agent such as atenolol is indicated.