We have investigated the relationship between the expression of bcl-2 and myc family genes in primary human neuroblastoma (NB) tumors and cell lines. Of 20 NB tumors examined, bcl-2 transcripts were expressed at variable levels in 16 tumors of all clinical stages. Of the 2 tumors with N-myc amplification, one expressed bcl-2 at a high level, whereas the other did so at a low level. In contrast, all NB tumors showed the expression of c-myc and/or N-myc transcripts. Similarly, of 9 NB cell lines with N-myc amplification examined, 6 expressed bcl-2 at high levels, whereas the other 3 expressed it at barely detectable levels. The 3 cell lines without N-myc amplification also expressed bcl-2 protein at high levels. All NB cell lines tested expressed either c-myc or N-myc protein. These data suggest that in NB, there is no significant association between bcl-2 expression and advanced tumor stages or N-myc amplification. The data also show that bcl-2 expression does not always coincide with myc expression in NB, suggesting that bcl-2- independent mechanisms may exist in the bcl-2-negative NB tumor cells in order to suppress the cell death promoting action of high myc expression.