In a search for specific serum markers with prognostic impact, we evaluated the clinical significance of IL-4, IL-7, and IL-8 as well as TNF receptor levels and soluble p53 in the serum of patients with untreated Hodgkin's lymphoma (HD). No elevations were observed for IL-4, while IL-7 and IL-8 were elevated in 15/52 (29%) and 21/78 (27%) patients, respectively. Soluble TNF receptors were detected in 16/29 patients (55%), and were significantly elevated in 6 (21%). P53 was detected in 21/33 (64%) patients. While IL-7 levels, detectable sTNF receptors, and p53 were not correlated with other obvious parameters, elevated IL-8 levels were associated with the presence of B symptoms (p < 0.002) and occurred more often in the nodular sclerosis form than in other histological subtypes (p < 0.02). Further investigations that correlate these serum parameters with the situation at the cellular level of an involved tissue will help to elucidate the enigmatic biology of HD.