Persistent airway inflammation is present in cases with asthma and in smokers with airflow obstruction. Isolated aggregations of lymphoid cells (IALC) may be sites of localized inflammatory cell activation. Their distribution and characteristics in cartilaginous airways were assessed in postmortem tissue from nonsmokers (n=10), smokers (n=9), and cases of nonfatal (n=10) and fatal asthma (n=10). IALC were present in 70-100% of cases, were more often in proximal than distal airways, and 80% were confined to the outer airway wall. IALC with area greater than 0.1 mm2 were more frequent in both asthma groups (p<0.001). Airways with IALC had increased airway dimensions and greater numbers of eosinophils and lymphomononuclear cells. Within IALC, T and B lymphocytes were segregated and comprised more than 90% of all cells. Proliferating, apoptotic, and antigen-presenting cells (Rel B+ and HLA-DR+) were less than 5%, 30-40%, and less than 1% of all cells, respectively, and were similar in each case group. Vascular structures were increased (p < 0.01) in cases of fatal asthma. These findings show that, even in nonsmoking cases and cases without asthma, IALC are common, show cellular organization, and are associated with airway wall inflammation and remodeling. It remains to be determined if IALC contribute to or result from persistent airway inflammation in asthma.