The efficacy of three different treatment protocols was compared: 1) simple chest tube drainage (Drain); 2) adjunctive intrapleural streptokinase CIP-SK); and 3) an aggressive empirical approach incorporating SK and early surgical drainage (SK+early OF) in patients with pleural empyema and high-risk parapneumonic effusions, This was a nonrandomized, prospective, controlled time series study of 82 consecutive patients with community-acquired empyema (n=68) and high-risk parapneumonic effusions (n=14). The following three treatment protocols were administered in sequence over 6 years: 1) Drain (n=29, chest catheter drainage); 2) IP-SK (n=23, adjunctive intrapleural fihrinolysis with 250,000 U.day(-1) SK); and 3) SK+early OP (n=30, early surgical drainage was offered to patients who failed to respond promptly following initial drainage plus SK), The average duration of hospital stay in the SK+early OP group was significantly shorter than in the Drain and IP-SK groups. The mortality rate was also significantly lower in the SK+early OP than the Drain groups (3 versus 24%). It was concluded that an empirical treatment strategy which combines adjunctive intrapleural fibrinolysis with early surgical intervention results in shorter hospitalstays and may reduce mortality in patients with pleural sepsis.