BACKGROUND.: To assess volumetric changes of human papillomavirus (HPV)-related lymph nodes (LN) before, during, and after a course of intensity-modulated radiation therapy (IMRT) ± chemotherapy. METHODS.: Each “pathologic” LN (≥1 cm) was contoured on the available diagnostic/planning CTs before, during each week, and after treatment. RESULTS.: Seventy-nine LNs in 50 patients were identified. Beyond the first week of treatment, 3 patterns of LN change were recorded: consistently shrinking LN (n = 33; 41.8%), inconsistently shrinking LN with temporary enlargement limited to the first week (n = 14; 17.7%), or also during the subsequent weeks (n = 32; 40.5%). Nodal density at planning is highly predictive of group assignment, with a larger mean density for consistently over inconsistently shrinking LNs (p = .009). Also, this grouping predicts the response at the end of treatment. CONCLUSION.: HPV-related LN behavior during IMRT is extremely variable but somewhat predictable on the basis of nodal density at planning.