The negative ino- and chronotropic effects of the new calcium antagonist, PY 108–068 (PY), were investigated and compared with several other calcium antagonists in paced left and spontaneously beating right atria of guinea pigs. The concentrations that decreased, by 25% (EC25), the contractile force and heart rate (HR), were determined. For PY, the concentration needed for the negative inotropic EC25, was 50 times higher than the concentration that diminished the HR by 25%. This ratio was also determined for the following calcium antagonists: nisoldipine, 27; verapamil, 2.8; gallopamil, 2.2; fendiline, 1.6; diltiazem, 3.4; and nifedipine, 0.35. The results obtained with PY and nifedipine were verified in rabbit right atria and papillary muscle. The separation between the two EC25, values was 23 for PY and 0.07 for nifedipine. Nitroglycerin had no effects on guinea pig and rabbit cardiac tissue in vitro. Conscious rabbits with chronically implanted catheters were used to determine if PY inhibits reflex tachycardia in vivo. The effects of nitroglycerin on blood pressure (BP) and HR served as a standard by which the effects of PY and nifedipine were compared. All three compounds lowered BP dose dependently and had similar initial effects on HR. While HR increased dose dependently with nitroglycerin and nifedipine, no such dose dependence was found with PY. PY thus inhibited reflex tachycardia in conscious rabbits. The wide separation between negative chronotropic and negative inotropic effects of PY implies that the calcium channels involved may be different. The selective action of PY could present a therapeutic advantage.