Established recently are two in vivo prostate tumor progression models in which subclones of the PC3M and LNCaP cell lines were selected for varying growth characteristics and metastatic potential after successive orthotopic implantation in the prostate of nude mice. In this study, we used comparative genomic hybridization (CGH) to compare the chromosomal abnormalities between the parental cell lines and their respective variants and to determine if specific chromosomal abnormalities can be identified that are associated with different growth properties. PC3M and its derivative cell lines PC3M-Pro4 and PC3M-LN4 shared gains of 8q22--qter, 10q21--q22, and Xq27--qter and loss of 13q33--qter. PC3M-Pro4, a derivative line that produced significantly larger tumors in the prostate, had a unique gain of 3q13. In contrast, PC3M-LN4, the derivative line that produced significantly larger metastatic tumors in the lymph nodes and had higher incidences of distant metastases, had a specific gain of 1q21--q22 and losses of 10q23--qter and 18q12--q21. In the second in vivo model, LNCaP and its derivative cell lines shared gain of 3q27--qter and loss on 13q21--qter. The derivative line that produced significantly larger tumors in the prostate, LNCaP-Pro5, had a unique gain on 13q12--q13. In comparison, LNCaP-LN3, a derivative line that had a significantly higher incidence of lymph node metastases and produced significantly larger metastatic tumors in the lymph nodes, had specific losses of 16q23--qter and 21q. Interestingly, some regions of loss (e.g., 10q23-->qter, 16q23-->qter, and 18q12-->q21) detected in the variant cell lines correlated well with abnormalities seen in clinical prostate cancer cases. Thus, our data suggest not only that these cell lines are relevant in vivo models for prostate cancer progression, but also that CGH is a valuable tool for uncovering chromosomal regions that are important for aggressive growth and metastasis of prostate cancer cells.