OBJECTIVE: Because HER-2/neu is overexpressed in one third of breast and ovarian cancers, we examined the effect of unconjugated monoclonal antibodies (ID-5, PB-3, TA-1) and an immunotoxin (TA-1-ricin) reactive with this protooncogene on the growth of breast and ovarian cancer cell lines. STUDY DESIGN: The tritiated thymidine incorporation assay was used to examine the effect of unconjugated antibodies on proliferation. A limiting dilution clonogenic assay was used to assess the effect of immunotoxin on cellular cytotoxicity. RESULTS: Scatchard analysis revealed that OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cells had approximately 10(4) HER-2/neu receptors per cell, whereas the SKOv3 and SKBr3 cell lines expressed 10(5) and 10(6) receptors per cell, respectively. Monoclonal antibody ID-5 caused significant inhibition of tritiated thymidine incorporation in SKBr3, SKOv3, and OVCA 420 cells (p < 0.002). The TA-1-rich immunotoxin significantly inhibited the clonogenic growth of only SKBr3 and SKOv3 cells. CONCLUSION: HER-2/neu may be a useful target for immunotherapy with unconjugated antibodies and immunotoxins in ovarian and breast cancers that overexpress this protooncogene.