Responses to 5-hydroxytryptamine (5HT) were compared in large [2.1–3.0 mm outside diameter (OD)], medium (1.5–1.8 mm OD) and small (0.5–1.0 mm OD) isolated canine coronary arteries. 5HT produced contraction of large and medium arteries, with the maximal response averaging 35.1 ± 4.0 and 21.0 ± 3.3%, respectively, of the contraction to 100 mM KCl. Endothelial removal increased the response to 5HT, with the maximal response averaging 43.6 ± 12.6 and 32.4 ± 7.5%, respectively, of the 100 mM KCl contraction. Small arteries did not contract significantly to 5HT in the presence or absence of endothelium. However, 5HT (10–6 M) contracted small arteries that were contracted with 30 mM KCl, averaging 130 ± 3% of the original contraction to KC1. This further contraction to 5HT was slightly potentiated by removal of the endothelium. We conclude that, unlike larger epicardial arteries, coronary arteries <1 mm OD are unresponsive to 5HT under resting conditions. Failure of small arteries to contract to 5HT cannot be explained by an inhibitory influence of the endothelium. However, 5HT enhances the contraction of small arteries to K+, and this response tends to be augmented by endothe