The value of immunoreactivity of antibodies against neuronspecific enolase (NSE), bombesin (GRP), and synaptophysin (SY 38) as markers for various human lung carcinoma has been assessed. One hundred-forty-two primary bronchus carcinomas (small cell anaplastic carcinoma, epidermoid carcinoma, adeno carcinoma, and large cell anaplastic carcinoma) were studied by the indirect immunoperoxidase method (PAP). SY 38 was found to react positively in 49/68 (79%) of the small cell anaplastic carcinoma (SCCL) and in 6/74 (8%) of the non-small cell carcinoma of the lung (NSCCL). Positive immunohistochemical data with antibody SY 38 showed in some cases an immunoreactive polypeptide of Mr = 40.000 obtained by immunoblotting similar in molecular weight as described for synaptophysin in other tumours. Reactivity of NSE was observed in 41/68 (61%) of the SCCL and in 8/74 (10%) of the NSCCL. Positive reactivity to GRP was similar to NSE in 42/68 (62%) of SCCL and in 7/74 (10%) of NSCCL. All cases of NSCCL reacting positively to SY 38 were found to react positively to NSE, and to GRP. Prognostic value of SY 38 was calculated vp = 0.71 for positive prediction and vn = 0.91 for negative prediction. The data indicate that SY 38 represents the broadest marker for neuroendocrine carcinoma of the lung since in addition to the majority of SCCL about 10% of NSCCL are recognized by the antibody SY 38.