We have used a new and rapid method to detect three variant forms of transthyretin (TTR): methionine for valine at position 30 (Met-30), serine for cysteine at position 6 (Ser-6) and methionine for leucine at position 111 (Met-111). By using an anti-transthyretin antibody and a centrifugal concentrator, transthyretin was isolated from plasma samples and analysed for variant forms by electrospray ionization mass spectrometry. Differentiation between homozygous and heterozygous transthyretin Met-30 and Met-111 posed no problems. However, a clear separation of transthyretin Ser-6 and Met-111 peaks in one patient with concordant Ser-6 and Met-111 mutations could not be achieved. The present method enables a quick and reliable detection of variant TTR. It can be used to screen families or small populations for abnormal TTR. Knowledge of TTR polymorphism and the variable expression of different amyloidogenic mutations should be taken into consideration when applying the methods in clinical practice.