|We determine phenotypic and cytological effects on pepper plant growth and development in response to systemic invasion by CMV and evaluate a CMV strain, mutated in the gene silencing suppressor gene, 2b, for its ability to infect pepper plants. We show that symptom development in CMV susceptible ‘Calwonder’ pepper plants occurred in three phases, each associated with a different host plant developmental stage. The initial expression of systemic symptoms occurred in young leaves in the form of a chlorosis over the basal half of the leaf at ca. 7 dpi. As new leaves emerged, ca. 12 dpi, these leaves developed a mosaic symptom expressed over the entire blade. Leaves expressing both symptom phases had high CMV titers. When the primary stem branched into two secondary stems, the leaves that developed on each secondary stem had a dull green appearance with varying degrees of distortion. These leaves accumulated significantly less CMV than leaves in the early symptom phases. Leaves that emerged after the leaf distortion phase were smaller and had a dull green color relative to comparable leaves on healthy plants. These newly emerging leaves had little or no detectable amounts of CMV. The apparent recovery from CMV infection in young leaves coincided with dramatically reduced and localized accumulations of CMV throughout the stem. CMV-infected plants were stunted relative to healthy plants. We show that the stunting occurred only along the primary stem during and shortly after chlorosis and mosaic symptom phases but not in secondary stems in the leaf distortion phase. The CMV 2b mutant was able to accumulate in inoculated leaves of pepper plants but did not establish a systemic infection. The accumulation of this mutant was significantly less in inoculated leaves than for the wild type parent. Mesophyll protoplasts isolated from ‘Calwonder’ leaves were inoculated with RNA isolated from the CMV 2b mutant or its wild type. Less CMV coat protein accumulated in CMV 2b mutant-inoculated protoplasts compared with those inoculated with the wild type. These findings indicate that the CMV 2b gene/protein is required for systemic infection of pepper plants and accumulation (translation/replication) at the cellular level.