We investigated the effect of Escherichia coli O127: B8 endotoxins on the adrenergic control of lipolysis in the human adipocyte. Adipose tissue was incubated in vitro with isoproterenol to stimulate the β-1 receptors, clonidine to stimulate the α-2 receptors, and theophylline to stimulate the subreceptor mechanism. Using a dual radioisotope technique, a lipolysis factor was calculated for each sample. The basal lipolysis factor was significantly ( P < 0.006) decreased 31% with endotoxin. β-1 adrenergic receptor stimulation (isoproterenol, 1 × 10 −8 to 1 × 10 −4 M) was significantly decreased an average of 31% with E. coli endotoxin. The β-1 receptor responsiveness was also significantly ( P < 0.02) decreased but not the receptor sensitivity. This indicated an alteration in the post β receptor mechanism. The various components of the post β-1 adrenergic mechanism were stimulated including the β-1 receptor, the G protein, adenylase cyclase, and the lipase phosphorylase. The results indicated a significant 24.2% reduction of the β-1 receptor and a 25.4% reduction in G protein stimulation. Thus the E. coli endotoxin effect on the β adrenergic mechanism is at the G protein. The endotoxin had no effect on the α-2 receptor stimulation nor the theophylline stimulation of the subreceptor lipolysis. This study indicates that E. coli endotoxin (O127:B8) decreases in vitro β adrenergic stimulation of human adipocyte lipolysis, and this effect can be partially reversed by theophylline.