A method and apparatus for segmenting medium access control (MAC) service data units (SDUs) creates enhanced MAC-es PDUs in the enhanced MAC-e/es sub-layer by concatenating MAC SDUs received from the logical channels. An enhanced transport format combination (E-TFC) selection entity controls the concatenation of MAC SDUs into enhanced MAC-es PDUs. When a MAC SDU is received that is too large to fit into a selected enhanced MAC-es PDU payload, a segmentation entity segments the MAC SDU such that the MAC SDU segment fills the remaining payload available in the selected enhanced MAC-es PDU. The enhanced MAC-es PDU is then assigned a transmission sequence number (TSN) and multiplexed with other enhanced MAC-es PDUs to create a single enhanced MAC-e PDU that is transmitted on the E-DCH in the next transmission time interval (TTI). A HARQ entity stores and, if necessary retransmits the enhanced MAC-e PDU when a transmission error occurs.