This study compared the individual responses to paralytic shellfish poisoning (PSP) toxins of Mya arenaria from two populations with contrasting histories of toxin exposure: Lepreau Basin, Bay of Fundy, New Brunswick (NB) (annual, recurrent PSP outbreaks) and Lawrencetown estuary, Nova Scotia (NS) (no previous toxin exposure). Clams were exposed to a high-toxicity strain of Alexandrium tamarense (PR18b; 60 pg STXeq/cell), under identical laboratory conditions for 2-3 weeks. Remarkable differences were observed in behavioral (burrowing capacity), and physiological responses (feeding rate on Alexandrium cells, tissue toxin uptake, and in vitro block of the action potential in isolated nerves exposed to saxitoxin). Percent burial (4% vs. 86% in NS and NB populations respectively after 24 h of exposure) and average clearance rates were significantly lower (4 to 8x) in NS than NB clams. Toxicities were significantly lower (up to 10-fold in viscera) in sensitive NS clams than in resistant NB clams. The former experienced cumulative mortality rates of up to 24%, which started after one week of toxin exposure, whereas NB clams exhibited negligible or no mortalities. Marked differences (more than an order of magnitude) were also observed between dominant phenotypes of the test populations (sensitive NS vs. resistant NB individuals, based on burrowing response at 24 h). These were observed during toxification (4-6 days of exposure), and after 16-20 day-depuration on non-toxic algae (in this case survivors were selected for testing). All NS clams exhibited partial nerve block at 10-6 g STX/ml, and most were fully blocked within 20 sec at 10-5. In contrast, most NB clams displayed no effect even at 10-5 and required 4 to 7 min. of exposure to induce full nerve block at 10-4 g STX/ml; some showed only partial block at 10-4 g STX/ml. Such intraspecific differences in sensitivity and toxin accumulation have important ecological and biotoxin monitoring implications, and suggest that genetic adaptation to toxins via natural selection of more resistant individuals may occur in areas recurrently affected by PSP.