Testosterone has immune-modulating properties and current in-vitro evidence suggests that testosterone may suppress the expression of the pro-inflammatory cytokines Tumour Necrosis Factor (TNF alpha), interleukin (IL)-1 beta and IL-6 and potentiate the expression of the anti-inflammatory cytokine IL-10. We report a randomised single-blind placebo-controlled crossover study of testosterone replacement (Sustanon 100) versus placebo in 27 men (age 62+-9years) with symptomatic androgen deficiency; total testosterone (4.4+-1.2 nmol/L) bioavailable testosterone (2.4+-1.1nmol/L). Compared to placebo, testosterone induced a reduction of TNF alpha (-3.1+-8.3 v 1.3+-5.2 pg/ml, p=0.01), IL-1 beta (-0.14+-0.32 v 0.18+-0.55 pg/ml, p=0.08) and an increase in IL-10 (0.33+-1.8 v -1.1+-3 pg/ml, p=0.01), the reductions of TNF alpha and IL-1 beta were positively correlated (rS = 0.588, p = 0.003). In addition a significant reduction in total cholesterol was recorded with testosterone therapy (-0.25+-0.4 v -0.004+-0.4mmol/L, p=0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and since total cholesterol is a cardiovascular risk factor and pro-inflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.