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Hope is significant to cancer patients in their struggle to find meaning in life as they adapt to the disease and its treatment. The purpose of this study was to test the effectiveness of a nurse telephone intervention to maintain hope and reduce symptom distress in chemotherapy patients. A conceptual framework, based on the hope models of Herth (1989) and Morse and Doberneck (1995), guided the study. Patient needs and resources were appraised using a Hope Assessment Guide (Penrod & Morse, 1997) that focused on behaviors related to coping with symptom distress, achieving goals, and mobilizing internal and external resources to maintain hope. A two-group randomized experimental design was used to test the effects of a nursing telephone intervention on hope and symptom distress in cancer patients (n = 100) receiving chemotherapy for the first time. Repeated measures of hope and symptom distress were made before the start of chemotherapy (baseline) and four times during the first two cycles of treatment. Mood states were measured at baseline and at expected nadir after the second cycle of chemotherapy. A total of three phone calls were made to each participant: those in the intervention group received a structured call from a nurse and those in the control group received brief reminder calls from a non-nurse. Hope was measured by the Herth Hope Index and Hope Visual Analog Scale, mood states by the brief Profile of Mood States, and symptom distress by the Symptom Distress Scale. Data were analyzed by descriptive statistics, t-test, Cronbach's alpha and analysis of variance. Patients in the telephone intervention group did not experience any statistically significant changes in either levels of hope or symptom distress compared to the control group. In addition, baseline measures of hope, symptom distress and positive mood states were significantly correlated in all subjects in the study. Because of study limitations, this correlation did not hold up over the course of treatment. A significant relationship was found between reduced symptom distress and positive mood states in all subjects of the study over two cycles of chemotherapy. These findings suggest that two measures of quality of life (mood state and symptom distress) were improved. Study results indicate a need to explore both hope-inspiring strategies and the management of symptom distress as mediators for enhancing quality of life in chemotherapy patients. Additional randomized testing in a larger sample of cancer patients is recommended. Further studies should also focus on the potential of meaningful nursing telephone interventions to improve health outcomes during chemotherapy treatment.