The phenotype of 165 gastrointestinal stromal tumours was studied by immunohistochemistry. In each case the phenotype was compared to the histological diagnosis. The phenotype was muscle in 49 tumours (30%), neural in 18 (11%), histiocytic in 20 (12%) and mixed in five (3%); 68 tumours (41%) were positive for vimentin only, four tumours had no markers and one tumour was positive for keratin only. Histologically, the tumours were classified as smooth muscle, probably smooth muscle, probably nerve sheath tumours or tumours of undetermined differentiation. In 30 histologically unequivocal muscle tumours, the phenotype was muscle in 28. Half of them, all benign, arose in the oesophagus or gastric cardia. Apart from this group, there was no correlation between phenotype, site of tumour and histological differentiation. Actin was a more sensitive muscle marker than desmin. With the exception of oesophageal tumours, the histological appearances alone could not establish a diagnosis of malignancy and were inadequate in evaluating differentiation. Immunohistochemical examination determined differentiation in 54% of the tumours, but this finding should be interpreted with caution in terms of histogenesis. It allowed us, however, to specify the differential diagnosis in 57 tumours in which the histological diagnosis was uncertain.