IgE-antibody reactivity to oysters and crustacea of sera from six oyster-sensitive, seven oyster- and crustacea-sensitive, and 12 crustacea-sensitive subjects was investigated. All six subjects with a history of only oyster sensitivity had minimal RAST reactivity (ratios 2 to 5) to extracts of raw or boiled oysters. Three of the seven oyster- and crustacea-sensitive subjects and six of the 12 crustacea-sensitive, oyster-tolerant or unexposed subjects had elevated RAST ratios to oyster (14 to 41). Generally, elevated oyster RAST correlated with skin prick test reactivity to oyster but not with total serum IgE levels. The oyster RAST values of the 19 crustacea-sensitive subjects (with or without oyster sensitivity) correlated with crustacea RAST reactivity (crab RAST, most significant; shrimp RAST, least significant). Rabbit antisera to crustacea extracts detected precipitating antigens present in extracts of raw or boiled oysters. Significant inhibition of the oyster RAST was obtained with oyster or crustacea extracts. These studies suggest that in the diagnosis of oyster sensitivity the RAST may not be useful and that oyster and crustacea contain common antigenic structures.