To study the origin of increased serum placental-like alkaline phosphatase (PLAP-like) activity in smokers, heat stable alkaline phosphatase activity was assayed from serum and bronchoalveolar lavage (BAL) fluid in 83 smoking and non-smoking patients. PLAP-like activity was increased in about 80% of the smokers, independently of the underlying lung disease. Isoenzyme activities in BAL fluid correlated (r = 0.631, p less than 0.001) with serum values. When adjusted for the albumin concentration, mean PLAP-like activity in BAL fluid was almost 1000-fold higher than that in serum, suggesting local synthesis of PLAP-like isoenzymes in the lungs. Although a direct dose-response effect was not observed, the values in serum and in BAL fluid tended to be higher in patients smoking over 10 cigarettes daily as compared to patients smoking less. In ex-smokers the results indicated that PLAP-like activity decreased to the level observed in non-smokers within 5 years after cessation of smoking. PLAP activity was L-leucine sensitive compatible with the Nagao-variant type of PLAP in almost all cases. In three patients the activity was due to the L-leucine resistant (true placental) isoenzyme.