We studied the effects of 13-cis-retinoic acid (13cRA) and 4-hydroxyphenyl-all-trans-retinamide (4HPR) on the proliferation of clonogenic human tumor colony-forming units (TCFU) from patient biopsies in soft agar. Continuous exposure (5 X 10(-6)M) to 13cRA and 4HPR reduced colony formation to less than 50% of control in 49% and 31% of cases, respectively. This suggests that these retinoids have antiproliferative activity against TCFU. Continuous exposure to 13cRA reduced the number of TCFU to 30% of control in 22.6% of cases while 4HPR reduced colony formation to less than 30% of control in only 10% of patients tested. Prospective in vitro/in vivo correlations for 13cRA indicated that clinical resistance was correctly predicted in 4 of 4 cases treated while clinical response was predicted in 2 of 2 cases (one minor and one partial response). These data suggest that retinoids may have modest antitumor effects and that inhibition of TCFU growth in vitro may be used to screen for such activity.