We made in vivo microvascular observations to simultaneously compare the actions of various direct vasodilators on the resistance and capacitance vessels without confounding systemic hemodynamic effects. The responses of gastric submucosal arteriolar and venular diameters to the topical application of 10(-7) 10(-5), and 10(-3) M of the vasodilators nitroglycerin (NTG), sodium nitroprusside (SNP), hydralazine (HYD), and adenosine (ADN), and acetylcholine (ACh) were studied in 6 rats for each agent using in vivo microscopy. The basal diameters of arterioles, 37 +/- 2 microns (mean +/- SE), were maximally dilated to 86 +/- 2 microns by 10(-3) M ADN, NTG, SNP or ACh, while with 10(-3) M HYD dilation was just 55%. The basal diameters of venules, 36 +/- 2 microns, were maximally dilated only to 51 +/- 1 micron by 10(-3) M ADN, NTG or SNP, while those by 10(-3) M HYD and ACh were 60 and 71%, respectively. We observed that: (1) NTG and SNP were the strongest arteriolar and venular dilators, but at low dose (10(-7) M), NTG was more effective than SNP. (2) Gastric submucosal venules had considerably less dilating capacity than arterioles. (3) ADN was as effective as NTG and SNP for both arteriolar and venular dilation at 10(-3) M. It was less potent at lower concentrations. (4) ACh was as potent as ADN, NTG and SNP in dilating arterioles, but it was notably less potent in dilating venules. (5) HYD was the weakest arteriolar and venular dilator among all agents studied, and its action on venules was slightly greater than that on arterioles.