1. Changes in muscle strength, vastus lateralis fibre characteristics and myosin heavy-chain (MyoHC) gene expression were examined in 48 men and women following 3 weeks of knee immobilization and after 12 weeks of retraining with 1866 eccentric, concentric or mixed contractions. 2. Immobilization reduced eccentric, concentric and isometric strength by 47 %. After 2 weeks of spontaneous recovery there still was an average strength deficit of 11 %. With eccentric and mixed compared with concentric retraining the rate of strength recovery was faster and the eccentric and isometric strength gains greater. 3. Immobilization reduced type I, IIa and IIx muscle fibre areas by 13, 10 and 10 %, respectively and after 2 weeks of spontaneous recovery from immobilization these fibres were 5 % smaller than at baseline. Hypertrophy of type I, IIa and IIx fibres relative to baseline was 10, 16 and 16 % after eccentric and 11, 9 and 10 % after mixed training (all P < 0.05), exceeding the 4, 5 and 5 % gains after concentric training. Type IIa and IIx fibre enlargements were greatest after eccentric training. 4. Total RNA/wet muscle weight and ty I, IIa and IIx MyoHC mRNA levels did not change differently after immobilization and retraining. Immobilization downregulated the expression of type I MyoHC mRNA to 0.72-fold of baseline and exercise training upregulated it to 0.95 of baseline. No changes occurred in type IIa MyoHC mRNA. Immobilization and exercise training upregulated type IIx MyoHC mRNA 2.9-fold and 1.2-fold, respectively. For the immobilization segment, type I, IIa and IIx fibre area and type I, IIa and IIx MyoHC mRNA correlated (r = 0.66, r = 0.07 and r = -0.71, respectively). 5. The present data underscore the role muscle lengthening plays in human neuromuscular function and adaptation.