Autologous activated macrophage (AAM) therapy is an adoptive cellular therapy based on ex vivo differentiation and activation of autologous peripheral blood monocytes. This study was undertaken to evaluate the tolerance, efficiency and biological effects of AAMs in chemoresistant progressive colorectal cancers. From January 1993 to May 1995, 15 patients were treated. Mononuclear cells were collected six times by weekly apheresis, cultured for 7 days, and activated with interferon-gamma. AAMs were then separated by elutriation and re-infused intravenously, with a mean total of 7.95 x 10(9) macrophages per patient. Clinical tolerance was good: toxicity consisted only of a World Health Organisation grade 2 fever after 28% of the infusions. Responses were not seen in the 14 evaluable patients, as expected with very bulky tumours: in 11, the tumours continued to progress, but disease was stabilised in 3 patients who experienced progression-free survival for 14, 12 and 12 weeks, respectively.