Chronic fluoxetine (FLX, 20 mg/kg, s.c.) reduces cardiac β‐adrenergic receptor (βAR) function in rats with congestive heart failure (CHF) and controls. To determine if FLX reduces βAR density or alters 5‐HT receptor (5‐HTR) density, 125I‐cyanopindolol (ICYP, 42 pM) binding was determined in left ventricular tissue of real‐ or sham coronary artery‐ligated rats, given daily FLX or vehicle for 5 wks. ICYP binding was assessed in the absence and presence of 1 μM 5‐HT (to determine 5‐HTR density), 1 μM CGP 20712A (to determine β2 receptor density), and 10 μM propranolol (for non‐specific binding). Ligated rats developed CHF (left ventricular end‐diastolic pressure: 29.7 ± 2.7 vs. 6.5 ± 2.1 mmHg, P<0.01). Serum fluoxetine and norfluoxetine levels did not differ between drug‐treated groups (278 ± 65 vs. 225 ± 31 ng/ml, 1,518 ± 176 vs. 1,440 ± 117 ng/ml, respectively). β1 and β2 receptor binding did not differ between groups. 5‐HTR density was increased in CHF compared to sham rats (2.99 ± 1.12 vs. 0.63 ± 0.27 fmol/mg, P<0.01) and decreased following chronic FLX treatment (2.99 ± 1.12 vs. 0.59 ± 0.43 fmol/mg, P<0.05). FLX reduces 5‐HTR‐, but not β‐receptor density in CHF rats. Supported by AHA 507025.