Prostate cancer resistance to castration occurs because tumours acquire the metabolic capability of converting precursor steroids to 5 alpha-dihydrotestosterone (DHT), promoting signalling by the androgen receptor and the development of castration-resistant prostate cancer(1-3). Essential for resistance, DHT synthesis from adrenal precursor steroids or possibly from de novo synthesis from cholesterol commonly requires enzymatic reactions by 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), steroid-5 alpha-reductase (SRD5A) and 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) isoenzymes(4,5). Abiraterone, a steroidal 17 alpha-hydroxylase/17,20-lyase (CYP17A1) inhibitor, blocks this synthetic process and prolongs survival(6,7). We hypothesized that abiraterone is converted by an enzyme to the more active Delta(4)-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor, providing an additional explanation for abiraterone's clinical activity. Here we show that abiraterone is converted to D4A in mice and patients with prostate cancer. D4A inhibits CYP17A1, 3 beta HSD and SRD5A, which are required for DHT synthesis. Furthermore, competitive androgen receptor antagonism by D4A is comparable to the potent antagonist enzalutamide. D4A also has more potent anti-tumour activity against xenograft tumours than abiraterone. Our findings suggest an additional explanation-conversion to a more active agent-for abiraterone's survival extension. We propose that direct treatment with D4A would be more clinically effective than abiraterone treatment.