The goal of our current study would be to attempt to combine bryostatin plus interleuken-2 as a second line therapy for the treatment of melanoma. This would be a phase II trial carried out in approximately 14 patients. During this trial, we would attempt to measure a number of biologic markers which would help us to understand both the mechanism of action of bryostatin and its ability to regulate the immune system. The goals of this study are therefore: 1) to carry out a single arm phase II study of bryostatin plus interleuken-2 in metastatic melanoma; 2) to examine lymphocyte function when these two agents are administered together (in collaboration with Dr. Rick Duke); 3) to measure the effects on gene transcription stimulated by bryostatin, specifically to study the effects of bryostatin on cell cycle regulated proteins, P21 and P27, as well as the levels of P16 in the tumor samples (in collaboration with Scalafani and Langan); 4) to study bryostatin pharmacology when this agent is given as a 72-hour continuous infusion using a unique bioassay; 5) to establish a murine model of melanoma to further examine whether bryostatin plus other agents would further enhance the anti-cancer effects of this compound. This proposal will examine novel treatment approach to melanoma. The eventual goal would be to add bryostatin to our armamentarium, to understand which drugs would complement the activity of bryostatin and to determine the biologic effects of this compound when administered to humans.