The interactions of amitriptylinoxide and various antidepressant drugs with different neurotransmitter and drug receptors were investigated by receptor binding studies. Amitriptylinoxide had less affinity than amitriptyline for most of the receptors studied. Half maximal inhibition of acetylcholine receptor binding occurred for amitriptylinoxide at 18 mumol/l (amitriptyline: 0.32 mumol/l). Comparing all studied antidepressants for muscarinic acetylcholine receptor binding, amitriptylinoxide had the weakest affinity of all tested tricyclic compounds. Also the affinity of amitriptylinoxide for alpha-receptor binding was about 60 fold less than that of amitriptyline. For all antidepressants investigated, the lowest affinities were found for benzodiazepine, opiate and beta-receptor binding. The weak affinities of amitriptylinoxide for various receptors may be responsible for its reduced side-effects, while it still retains potent antidepressant properties by stabilising the amitriptyline-level in the brain.