Previous in vitro studies demonstrated that acetaldehyde (ACHO) is able to produce specific morphological alterations related to the foetal alcohol syndrome. Intracellular reduced glutathione (GSH) has been shown to modulate the embryotoxicity elicited by various chemicals in vivo and in vitro. The present study evaluates the role played by endogenous and exogenous GSH and its precursor N-acetylcysteine (NAC) on the embryotoxicity induced by ACHO using the rat whole embryo culture system. In the first experiment embryos at gestation day (GD) 9.5 were cultured in rat serum medium for 18 hr in the presence of 1 mm l-buthionine-S,R-solfoximine (BSO), a specific inhibitor of GSH synthesis. Following pretreatment, conceptuses were cultured for a further 30 hr in the presence of 30 mug ACHO/ml. Pretreatment with BSO significantly enhanced the embryotoxic effects of ACHO and markedly reduced the GSH level only in the yolk sac. In the second experiment GSH or NAC (8 mum) were added to the medium by two different procedures in an attempt to reduce ACHO-induced embryotoxicity. In one case the embryos were exposed to ACHO for 8 hr and then transferred to media containing NAC or GSH for the remaining time of culture (22 hr); in another, the embryos were maintained for the entire culture period (30 hr) in a medium containing ACHO plus NAC or GSH. Only in the first case did exposure to NAC significantly reduce the frequency of abnormal embryos; in the second case the concurrent exposure to ACHO and thiols only marginally reduced ACHO-induced effects. Significant variations in the GSH content were recorded only at the level of the yolk sac. This result suggests that the yolk sac GSH can play a major role in the protection of the embryo against the toxic effects produced by xenobiotics.