Vesicular stomatitis virus (VSV), when reproduced in human tumor cell lines, assembled a specific subset of cell-derived proteins. These were detected by 35S]methionine labeling of cells prior to infection and subsequent immunoprecipitation of VSV grown in these cells, as well as by direct immunoprecipitation of labeled cell extracts with antiserum directed against the VSV-assembled proteins. Their molecular weight (Mr) ranged between 15K and 180K; the larger proteins were glycosylated. Two of the major protein species (gp88 and gp130) were common to all four cell lines used (HeLa-cervical carcinoma, T47D-breast carcinoma, and HMB2 and SK1477-two melanoma cell lines). Proteins of other molecular weights were detected only in one or two of the cell lines. The melanoma cell lines (even in the absence of VSV) shed large particulate material which had contained the same spectrum of proteins that were assembled by VSV. The major protein component had an Mr of 30K. Some of the VSV-assembled proteins might possibly serve as specific tumor markers. It is also conceivable that the proteins assembled by VSV as well as the large particulate material might be products of defective endogenous human retroviruses.