In 1996 two chemotherapy agents were introduced by the U.S. Food and Drug Administration (FDA) with indications for the gastrointestinal malignancies for advanced colon and pancreatic cancers. The agents approved were irinotecan hydrochloride (CAMPTOSAR Injection, Pharmacia & Upjohn Company, Kalamazoo, MI; also investigated under the name CPT-11) for the second-line treatment of metastatic colorectal cancer, recurrent or relapsed, after 5-fluorouracil (5-FU)-based therapy, and gemcitabine hydrochloride (GEMZAR for injection, Eli Lilly and Company, Indianapolis, IN; also referred to as dFdC) for first-line treatment of locally advanced and metastatic cancer of the pancreas. Irinotecan and gemcitabine, with demonstrated activity in colorectal and pancreatic cancer, respectively, are generally well tolerated and can be administered safely on an outpatient basis. Clinically relevant activity is documented for both single agents. Therapy-related side effects are manageable with appropriate monitoring and intervention, and reversible with dose modification or discontinuation. This article is one of a two-part series on new chemotherapeutic agents for gastrointestinal malignancies. The first in the series, this article addresses the agent irinotecan hydrochloride (CAMPTOSAR Injection). The second article, appearing in a subsequent issue, will review gemcitabine hydrochloride (Gemzar for Injection). Both articles review the current clinical use, safety profile, and key patient management guidelines for these new and novel cytotoxics. As clinical and investigational use of irinotecan and gemcitabine increases, the oncology nurse and other members of the health care team will need to anticipate potential treatment associated toxicities and be knowledgeable in their early identification and management. As patient advocates, oncology nurses play a key role in treatment outcome and related quality of life through expert patient education, symptom recognition, and intervention individualized to patient tolerance. This first article of the series addresses irinotecan, which in 1996 was approved for the second-line therapy of metastatic colorectal cancer, recurrent or elapsed, after 5-fluorouracil (5-FU).