This study evaluated the toxicokinetics of a saxitoxin (STX) analog, [3H]saxitoxinol (STXOL), in rats. [3H]saxitoxinol (18.9 microCi/kg body weight) was administered iv to male Wistar rats via the penile vein. After injection, [3H]STXOL disappeared rapidly from plasma (t 1/2 = 29.3 min), and 75% of the radiolabel was cleared from plasma within 2 hr. Radioactivity associated with red blood cell membranes was inversely related with the radioactivity associated with hemoglobin, suggesting internalization of STXOL. Distribution of [3H]STXOL, 48 hr after iv exposure, showed that muscle tissues retained 91.2 +/- 7.1%, liver 63.7 +/- 3.8%, heart 17.4 +/- 1.6%, and lung 9.2 +/- 0.8% of the residual dose. High-performance liquid chromatography (HPLC) analysis for saxitoxinol showed three to four major radiolabeled peaks for each of these tissues. By 48 hr, radiolabel associated with the saxitoxinol peak decreased 95% in lungs, heart, and kidneys, with a concomitant increase in unidentified, more polar peaks. No STXOL metabolites were detected in the urine from these animals. Radioactivity accumulation in the brain increased to a maximum of 162% at 8-hr postexposure, compared to values obtained at 10 min, then gradually declined to 148% by 48 hr. HPLC analysis of brain extracts showed that the relative percentage of radioactivity associated with parent toxin gradually decreased, with a concomitant rise in the levels of more polar peaks. Similar results were obtained for spinal cord. The data suggest that saxitoxinol was rapidly cleared from most of the peripheral organs and was little, if any metabolized by muscle cells.