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Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, is a protein kinase C (PKC) modulator which has shown both preclinical and clinical activity in lymphoid malignancies. We conducted a phase II trial of bryostatin 1 administered at a dose of 120 microg/m2 by 72-h continuous infusion every 2 weeks in patients with relapsed multiple myeloma. Treatment was well tolerated with myalgias constituting the primaray toxicity. There were no responses in nine evaluable patients. The preclinical anti-lymphoid activity is strong enough to support further exploration of bryostatin 1 in different schedules and in combination therapy for multiple myeloma.