This study identifies early, postmetamorphic soft-shell clams, Mya arenaria, as the life-history stage most susceptible to effects of blooms of paralytic shellfish poisoning (PSP) toxin-producing Alexandrium spp. Laboratory experiments used progeny from predominantly susceptible (naïve) or resistant (annually exposed) NW Atlantic populations. Growth and survival of toxified veliger larvae did not differ from those fed nontoxic algae. In contrast, postlarvae (4-12-mm shell length) from both populations exposed to a highly toxic Alexandrium tamarense isolate (, 100 cells mL 21 , 64-69 pg saxitoxin equivalents [STXeq] cell 21 ) suffered burrowing incapacitation, toxin accumulation, and mortalities within 1 week of toxin exposure. These effects were greater and occurred sooner in the naïve population. Short-term toxification in the laboratory caused a significant shift in the genotypic composition of this population, determined with a molecular marker for sodium-channel resistance. Clams with the sensitive genotype were selectively eliminated relative to resistant or heterozygote clams. Ingestion of toxic cells (too large for larval capture) is thus required to elicit toxic effects. Exposure to mixed, toxic, and nontoxic algal suspensions demonstrated that adverse effects to fitness (survival and growth) were dose-dependent, occurring only at $ 50 cells mL 21 of the isolate used (PR18b). Paralysis and thus increased predatory risk occurred even at 10 cells mL 21 . Postlarvae , 12 mm, which can co-occur with red tides throughout the Atlantic range of M. arenaria, were more susceptible to PSP than large (. 30 mm) juveniles. Natural selection for resistance in Atlantic populations will thus vary latitudinally with the timing, duration, and intensity of toxic blooms.