Thirty-six neuroblastomas were studied to determine the clinical significance of the N-myc gene product, N-myc, and the ras gene product, p21. The expressions of both gene products were analyzed immunohistochemically using formalin-fixed paraffin sections. Neuroblastoma cells were positive for N-myc expression in 13 cases and for p21 expression in 19 cases. N-myc expressions showed no significant relation to any clinical prognostic factor, whereas p21 expression was well correlated with clinical staging and Shimada's classification. There was a tendency for p21 expression to be low in N-myc(+) tumors, whereas p21 expression was frequently detected when N-myc expression was absent. The survival rate for N-myc(-) patients was significantly higher than for N-myc(+) patients (P < 0.01). The survival rate for p21(+) patients was significantly higher than for p21(-) patients (P < 0.001). In addition, N-myc(+) and p21(-) patients showed a strong tendency towards a poor prognosis, whereas a combination of p21(+) and N-myc(-) indicated a good prognosis (P < 0.01). The results suggest that expressions of N-myc and p21 detected by immunohistochemical staining could be among the most reliable prognostic indicators in neuroblastoma patients.