Eighty-eight primary and secondary lung tumor specimens were subcutaneously transplanted into athymic nude mice. One third of all carcinoma specimens yielded tumor growth. Success rates were highest if fresh tumor pieces or fresh or frozen cell suspensions were implanted or injected. More than half of squamous cell and adenocarcinoma xenografts showed a lower degree of differentiation than the original tumor. The degree of dedifferentiation led to the diagnosis of large cell carcinoma by light microscopical criteria in 4 of these cases. All small cell carcinoma xenografts showed intermediate-cell type morphology irrespective of the cell type of the original tumor, and all large cell carcinoma xenografts showed features similar to the original tumor. Tumor latent periods were approximately twice as long during the first nude mouse passage than subsequent passages, and tumor doubling times remained stable during serial passages. We conclude that the large cell lung carcinoma subtype is a mixed bag of tumors and includes highly undifferentiated squamous cell and adenocarcinomas, that the small cell carcinomas remain in that histologic subtype during xenotransplantation, and that lung carcinoma xenografts display stable morphologic and kinetic features during serial xenotransplantation. Nude mouse xenografts may serve an in vivo model to study the biologic relationship of non-small cell lung carcinomas.