We recently described a high throughput receptor binding assay for paralytic shellfish poisoning (PSP) toxins and its use for detecting toxic activity in extracts of various shellfish species and Alexandrium spp. cultures. The efficiency of this assay has been increased dramatically through reformatting to accommodate microplate scintillation technology, yielding a turn around time of 4 hours for a 96-well plate. In collaboration with colleagues at NEN Life Science Products(Boston, MA, USA), we have also validated the use of 3H-tetrodotoxin (TTX) as an alternative radioisotope to the conventionally employed 3H-saxitoxin (STX). Either 3H-TTX or 3H-STX can be used interchangeably with no compromise in assay performance, which allows for greater flexibility in response to restricted isotope availability. Efforts are now being focused on demonstrating the range of applications for which this receptor assay can provide data comparable to the more time consuming, technically demanding HPLC analysis of PSP toxins. To date, we have compared the results of both methods for a variety of sample matrices, including different genera of PSP toxin producing dinoflagellates(e.g., Alexandrium fundyense, r2=0.8727, n=17), size-fractioned field samples of Alexandrium spp. (20-64 mm; r2=0.9998, n=7) as well as its associated zooplankton grazer community (200-500 mm; r2=0.4715, n=10), and contaminated human fluids (r2=0.9661, n=7) from a PSP outbreak. Our findings show that the saxitoxin equivalent values generated by receptor assay for all but the zooplankton samples are in very close quantitative agreement with those produced by HPLC, yet the former can be obtained in considerably less time. While the PSP receptor binding assay does not provide information on toxin composition, it does represent an effective means of rapidly assessing toxicity in sample matrices from the laboratory and the field, as well as identifying samples for more detailed analysis by HPLC.