Human rhinoviruses (HRV) cause acute upper respiratory illness. The frequency of HRV-associated illnesses appears greater when PCR assays are used to detect rhinoviruses. The present study performed PCR-based detection of HRV upon entry of subjects into respiratory syncytial virus and parainfluenza type 3 vaccine trials when subjects were symptom-free and upon subsequent development of clinical symptoms of respiratory illness during the trial. The background of HRV PCR positivity in symptom-free individuals (30/139 [22%]) was only slightly lower than in those with respiratory illness (28/77 [36%]). For subjects with multiple samples, it was estimated that HRV was detectable by PCR for approximately 100 days before, during, and after clinical symptoms were documented. PCR is a remarkably more sensitive method of detecting HRV than is tissue culture. The presence of HRV RNA may not always reflect an association with infectious virus production. The limited association of HRV RNA with illness suggests caution in assigning causality of HRV PCR positivity to clinical symptoms of respiratory illness.Over 100 serotypes of human rhinoviruses (HRV), members of the family Picornaviridae, have been identified through community surveillance of respiratory illness (19). HRV has traditionally been identified by growth in tissue culture, as characterized by cytopathic effect. HRV are differentiated from enteroviruses by the capacity to grow at 33°C and acid lability. HRV are responsible for a substantial proportion of upper respiratory illnesses (19). Because infectious HRV are difficult to recover from clinical samples, it has been postulated that HRV may be responsible for other respiratory illnesses currently of unknown etiology (1,8,18,24). The fact that less than 1 50% tissue culture infectious dose of HRV caused an experimental human rhinovirus infection (5) suggests that tissue culture may not efficiently detect HRV. Recent reports suggest that PCR detection extends the scope of HRV illness to include lower respiratory tract illness (10) and establishes a strong association between rhinovirus and exacerbations of asthma (12,26). HRV has been shown to replicate in cells of both the upper (14, 27) and lower (21) respiratory tracts and can grow at the higher temperature of the lower respiratory tract (22).However, more limited studies have detected HRV by PCR in 12 to 20% of asymptomatic children and in a relatively high percentage of adenoid and tonsillar tissues, suggesting that identification of HRV by PCR may not necessarily confirm it as the etiologic agent (16,20,23,25). Identification of rhinovirus infection by PCR may not be accompanied by a serologic response, an unusual occurrence with most symptomatic respiratory viral infections (4).Clinical studies evaluating the safety of live, attenuated strains of respiratory syncytial virus (RSV) (17, 29) and parainfluenza virus type 3 (PIV3) (3) have recently been carried out with adults and children as young as 4 weeks of age. Nasal wash samples were collected from sympt...