Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric alpha-helix into beta-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.