The relaxing effect of nitrendipine and D600 on isolated ring segments of calf retinal resistance arteries (i.d. ca. 200 microns) contracted with prostaglandin-F2 alpha (PGF2 alpha) or high potassium solution was studied. The vessel response to both PGF2 alpha and potassium stimulation was dependent on extracellular calcium. Removal of extracellular calcium reduced the vessel response to PGF2 alpha and potassium by 85% and 98%, respectively (P less than 0.01). Both calcium antagonists induced a concentration dependent relaxation of PGF2 alpha pre-contracted vessels with = -log[IC50(M)]-values of 8.01 and 7.13 for nitrendipine and D600 (P less than 0.05), respectively. The calcium antagonists were equieffective in relaxing the vessels amounting to 33% for nitrendipine at 10(-6) M and 37% for D600 at 10(-5) M. Further analysis of the data revealed that the nitrendipine induced relaxation of the PGF2 alpha response was linearly correlated with the internal lumen diameter of the vessels. No correlation was found for the D600 induced relaxation. At the highest concentrations of nitrendipine, 10(-6) M, and D600, 10(-5) M, the potassium induced response was reduced by 94 and 75%, respectively. The results show that calcium antagonists only partially relax retinal resistance arteries contracted with PGF2 alpha although the vessels are dependent on extracellular calcium for active force generation. Calcium must therefore be activated by PGF2 alpha through other pathways than those blocked by calcium antagonists.