To determine the efficacy of and clinical response to several pharmacologic agents for treatment of idiopathic hypertrophic cardiomyopathy in cats, 17 symptomatic cats were randomized to treatment with either propranolol, diltiazem, or verapamil. Clinical, laboratory, radiographic, electrocardiographic, and echocardiographic data were obtained before treatment and after 3 and 6 months of chronic oral therapy. Too few of the cats receiving propranolol or verapamil survived long enough to obtain long-term data needed to make statistical comparisons between groups. However, all 12 cats ultimately treated with diltiazem became asymptomatic, and no adverse effects from this drug were noted in any of these cats. Treatment with diltiazem was associated with a significant reduction of pulmonary congestion assessed radiographically (P less than 0.01), and improved ventricular filling based on echocardiographic measurements of left atrial size (P less than 0.05), left ventricular internal diastolic dimension (P less than 0.05), and relaxation time index (P less than 0.001). There was also a drug-related improvement in jugular venous oxygen tension (P less than 0.001) and blood lactate concentration (P less than 0.01) suggesting improved peripheral perfusion in the cats receiving diltiazem. The results indicate that diltiazem provides an effective and apparently safe treatment for the management of feline hypertrophic cardiomyopathy.