The temporal relationship between glycosaminoglycan (GAG) accumulation and amyloid deposition was determined in two models of amyloid induction. In the first model amyloid was induced rapidly using amyloid-enhancing factor and AgNO3 as an inflammatory stimulus. In the second model amyloid was induced by daily injections of azocasein. Congo red staining was used to demonstrate amyloid, and both the sulfated Alcian blue and Alcian blue (pH 5.7)-MgCl2 methods were used to demonstrate GAGs. In the rapid model, amyloid was first detected in the splenic perifollicular areas 36 hours after induction. The initial presence of GAGs was also seen at 36 hours and in the exact locale where the amyloid was found. Amyloid was first seen in the liver about the central veins at 48 hours. GAGs in the liver appeared coincidentally with and in the same location as the amyloid. In the traditional model (azocasein injections) amyloid did not appear in the spleen until day 6 to 7, again with coincidental GAG deposition. The present study shows that amyloid-associated GAGs appear in the tissues together with the AA protein and are not a function of the tissue type. The appearance of the GAGs is also not a function of the nature of the inflammatory agent or its length of action but appears to be part of the process involved in the deposition of the AA protein.