Stromal tumours of the gastrointestinal tract remain a persistent source of controversy with regard to both their proposed lines of differentiation and the difficulty in predicting their biological behaviour. We have examined 60 cases with a panel of seven antibodies directed at the identification of smooth muscular or neural differentiation. In our hands, 36 per cent of cases showed neural differentiation (although only 6.6 per cent expressed S-100 protein); 31 per cent appeared smooth muscular; 20 per cent manifested bidirectional differentiation; and 13 per cent were negative for all the markers used. Histological appearances do not reliably reflect immunophenotype. We have attempted to correlate immunophenotype with the site of the lesions and with their clinical behaviour. Mean follow-up of 5 years was obtained in 42 cases. Tumours with a neural phenotype have the best prognosis. Gastric tumours expressing both desmin and smooth muscle actin (in the absence of other markers) with up to 4 mitoses per 30 HPF behave in a benign fashion. Larger studies are required to substantiate the value of immunophenotyping this complex group of tumours.