Tumor cell migration is a fundamental process of metastasis. Pertussis toxine inhibits lysophosphatidic acid related cell migration by ADP-ribosylation of G proteins. We examined the influence of pertussis toxine (PTX) on progression and metastasis of the human hormone-insensitive prostate cancer cell line PC-3 after orthotopic implantation in nude mice. In 30 athymic male nude mice (NMRI) 5x10(5) PC-3 cells were injected into the dorsal prostate. After 7 d 15 mice received a total of six intraperitoneal injections of 5 micro g PTX/100 g body weight at an interval of 4 d. The other 15 mice received phosphate buffered saline and served as control. All mice were killed at 37 d followed by macroscopical and histological evaluation of local tumor growth and metastasis. In the control group tumorigenicity was 100% (15 out of 15). Mean weight of the tumor bearing unit of prostate and seminal vesicles was 541 mg (243-763 mg). The rate of positive lymphnodes was 100% with a mean transversal diameter of 3.9 mm (1.2-5.4 mm). In the PTX group local take rate was 100% with a mean weight of 251 mg (88-478 mg) (P two sided <0.0001). The rate of positive lymphnodes was 60% (9 out of 15) (P=0.017) with a mean transversal diameter of 2.3 mm (1.0-4.5 mm). PTX following orthotopic implantation of the human hormone-insensitive PC-3 cell line significantly reduces local tumor growth as well as metastasis to locoregional lymphnodes.