Lesions of the nucleus basalis magnocellularis in rats have been used to investigate functions of the extrinsic cortical cholinergic system which originates from these neurons. These lesions also produce extensive non-specific subcortical damage and associated regulatory and neurological impairments, causing doubt about the specificity of consequent functional impairments. Here, nucleus basalis magnocellularis lesions made with four different neurotoxic amino acids (kainic acid, ibotenic acid, N-methyl-D-aspartate, and quisqualic acid) have been compared. Quisqualic acid produced less subcortical damage and lesser neurological and regulatory impairments than the other toxins at doses that produced comparable cholinergic deafferentation of the neocortex, as assessed both histologically and biochemically. This suggests that these impairments are non-specific rather than specific consequences of cholinergic cell loss. The effects on learning a spatial navigation task were more ambiguous, suggesting the involvement of both cholinergic and non-cholinergic systems. Impairment of a passive shock avoidance task was as great following quisqualic acid as the other neurotoxins, which may suggest a more direct relationship specifically with the decline in cortical cholinergic activity. It is concluded that in the absence of availability of a specific cholinergic neurotoxin, quisqualic acid produces less non-specific neuroanatomical and neurological side effects than the more widely used toxins N-methyl-D-aspartate, kainic acid or ibotenic acid.