Noscapine is an alkaloid derived from opium, which lacks sedative, euphoric, analgesic or respiratory depressant properties. Antitumor activity of Noscapine has been demonstrated both in vivo, against human lymphoid tumor cells, and in vitro, in human tumors implanted in athymic mice. Noscapine induces conformational changes in tubulin, which results in altered microtubule assembly. In this Phase I trial, cohorts of subjects with relapsed/refractory non-Hodgkin’s lymphoma (NHL) or chronic lymphocytic leukemia (CLL/SLL) were treated at three different dose levels of total daily doses of 1 g, 2 g, and 3 g. At each dose level the drug was administered orally on a three times a day schedule. The total duration of treatment was 49 days. Results: Twelve subjects with a median age of 65 years (range 38–71) have been accrued. Four subjects had CLL/SLL, 2 had mantle cell lymphoma, one had follicular grade III, 4 had DLC, and one had lymphoplasmacytic low grade lymphoma. 10 subjects are evaluable for response. Partial response was seen in 1 subject with follicular grade III disease. The duration of this PR is 56+ months. Stable disease was seen in a case of mantle cell lymphoma (duration 30 days) and a case of DLC (duration 77 days). The remaining 7 subjects had progression of disease. Noscapine has been well tolerated, with no grade 3 or 4 hematological toxicities. One grade 3 neurotoxicity consisting of depressed level of consciousness was experienced at the 3 g dose level. We conclude that a larger study of Noscapine is warranted to evaluate the efficacy of the compound in patients with lymphoma. The oral formulation, suggestion of efficacy and relative lack of toxicity make Noscapine an attractive candidate for further study.