Tissue levels of the alpha subunit of G protein G(o) (G(o) alpha) were measured in solid tumors from pediatric patients by immunoassay. G(o) alpha concentrations were determined in the supernatant obtained by centrifugation of tissue homogenates prepared in the presence (total G(o) alpha) or absence of 2% sodium cholate (soluble G(o) alpha). Mean G(o) alpha concentrations (total G(o) alpha and soluble G(o) alpha) in neuroblastomas (7 ganglioneuromas, 13 ganglioneuroblastomas, and 50 neuroblastomas) were over 50-fold higher than those in other solid tumors from pediatric patients (n = 13). Mean total G(o) alpha and soluble G(o) alpha concentrations were 207.0 +/- 166.0 (SD) ng/mg of cholate-extractable protein and 58.6 +/- 47.0 ng/mg of soluble protein, respectively, in the neuroblastoma group (n = 70). Total G(o) alpha concentration decreased with disease stage and was strongly correlated with outcome in patients with neuroblastoma. The mean total G(o) alpha concentration in tumors from younger patients (<1 year old) was 297.0 137.0 ng/mg of cholate-extractable protein, significantly higher than in tumors from older patients (140.0 +/- 155.0 ng/mg cholate-extractable protein, P < 0.0001). These results suggest that total G(o) alpha levels in neuroblastoma may indicate the degree of malignancy.