A mixture of sodium nitroprusside (SNP) and trimethaphan, empirical 1:10 weight ratio, has been advocated to decrease untoward side effects of SNP when used to induce hypotension during anesthesia and operation. The purpose of this study was to investigate the effects of various ratios of mixtures of SNP and trimethaphan on heart rate (HR), renal sympathetic nerve activity (RSNA), and renal artery blood flow to find the best ratio of SNP and trimethaphan for producing induced hypotension. Five mixtures with different ratios of SNP and trimethaphan, as well as each drug alone, were given intravenously to mongrel dogs in amounts adequate to achieve a stable mean arterial blood pressure of 75 +/- 5 mm Hg. Sodium nitroprusside alone significantly increased HR (163% +/- 14.5%) and RSNA (222% +/- 24%). Trimethaphan alone significantly decreased RSNA (11.6% +/- 4.5%). There were significant positive correlations between SNP-to-trimethaphan ratios and percent changes in HR (r2 = 0.301, P less than 0.01) and in RSNA (r2 = 0.648, P less than 0.01). Renal artery blood flow was well maintained with all ratios. Sodium nitroprusside and trimethaphan interacted synergistically to produce hypotension. However, they antagonize each other in their effects on arterial baroreflex-mediated changes in HR and RSNA. According to linear regression lines, HR changed least with a SNP-to-trimethaphan ratio of 1:5, and RSNA changed least with SNP-to-trimethaphan ratios of 1:2.5 and 1:5. Our results indicate that mixtures of SNP and trimethaphan in ratios of approximately 1:2.5 to 1:5 may produce induced hypotension with stable reflex sympathetic nerve activity.