Little is known about the frequency, severity, and course of symptoms experienced by patients receiving radiotherapy (RT). For this descriptive study, 1129 patients with a variety of cancer diagnoses completed a 12-item Symptom Inventory (SI) at the start of RT; 419 of these patients also completed the SI weekly for an additional 4 weeks (five data points). Eighty-four percent of the 1129 patients were already experiencing symptoms when treatment began. All symptoms significantly increased in frequency over a typical 5 week RT course (all Ps<0.001). Skin problems showed the largest increase. The most common symptoms (fatigue, drowsiness, and sleep problems) were also the most severe. Female patients and patients younger than the median age (59 years) reported significantly more symptoms than males and those 59 years or older. Symptom frequency and severity varied significantly by cancer diagnosis. Improved understanding about the time course and dose response of radiation-induced toxicity will permit more accurate presentation of side effect risk at the time patient consent is obtained.