The pathogenesis of myotonic dystrophy (DM) and the function of the product of the DM gene, myotonin protein kinase (Mt-PK), and its relationship to the disease are uncertain. To gain insight into the function of Mt-PK we studied the effect of decreasing the levels of Mt-PK in cultured human myoblasts. Myoblasts were transfected with an anti-sense oligonucleotide (ODN) targeted to the translation initiation site of DM mRNA which resulted in about 76% reduction in the levels of Mt-PK protein. A large percentage (about 48 to 90%) of myoblasts transfected with this oligonucleotide (but only about 2 to 23% of myoblasts transfected with a control oligonucleotide) underwent apoptosis within 24 h. To further substantiate these results we delivered a specific antibody to Mt-PK into the myoblast cells using a lipid carrier to inhibit its function and show that this resulted in apoptosis in 57 to 72% of the cells within 24 h. These results suggest that decreased levels of Mt-PK may contribute to muscle pathology in DM by leading to apoptosis of muscle cells.