I Antagonism between either the dihydropyridine calcium agonist, Bay k 8644, or high external Ca2" and the calcium antagonists, nifedipine, verapamil and diltiazem, and Mn2" was investigated in canine isolated ventricular trabeculae. 2 Bayk 8644 (107-l0-M) produced a slowly developing increase in developed tension which reached a maximum at 10-6 M. A small decrease in the positive inotropic effect of Bay k 8644 at I05 M was probably due to the negative inotropic effect of the solvent, 0.5% ethanol.3 Bay k 8644 (10-7-10 5M) produced a rightward parallel shift of the concentration-response curves for the negative inotropic effects of nifedipine (10 -10 -M) and verapamil (10-7-3 x 10-5 M). The slopes of the Schild plots were -0.92 for nifedipine (pA2 value = 6.58) and -0.48 for verapamil. 4 Bay k 8644 (10-6 and 10I-5 M) produced only a slight rightward shift of the concentration-response curves for the negative inotropic effect of diltiazem (10-7-3 x 10-5 M) and did not affect the negative inotropic effect of Mn2+ (10--10-2 M). 5 Addition of 2.5 x 10I-3 M Ca2+ (5.05 x 10 3M Ca2+) to the medium produced a greater maximum positive inotropic effect than Bay k 8644. The concentration-response curves for the negative inotropic effects of nifedipine, verapamil and diltiazem obtained under these conditions were not essentially different from those under control conditions (2.55 x 10-3 M Ca2+).