The effect of hormonal modulation on the response of human prostate cancer cell lines to photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was studied. Two cell lines, one responsive to androgens (LNCaP) and the other non-responsive (PC-3), were used. Fetal bovine serum was depleted of steroid hormones by stripping with charcoal-dextran, and then resupplied with known concentrations of the androgen 5alpha-dihydrotestosterone (DHT) or the estrogen estradiol. It was found that LNCaP cells alone increased growth rate in response to both added hormones, but only androgen had an effect on PDT treatment. LNCaP cells pretreated with 10(-7) M DHT and then 1 mM ALA accumulated 70% more PpIX, compared to cells pre-treated with 10(-12) M DHT. Exposure of the cells treated with high DHT and ALA to 630 nm light led to an 85% decrease in the number of surviving cells compared to the low DHT treated group. The uptake of 14C-ALA was increased with high DHT treatment of the cells, consistent with the above data. No effect of hormones was seen with PC-3 cells or with either cell line and the exogenous photosensitizer benzoporphyrin derivative.