There are several thread on this forum on the topic that indicate causes including the port being blocked, possibly by a 
firewall/AV product (Comodo did this to me years ago after an update 
installed a new "feature"), a change by TalkTalk in port or authentication, a configuration issue in the SMTP host configuration in Pegasus 
Mail.
First verify that the SMTP host configuration in Pegasus 
matches the current TalkTalk SMTP connection requirements (server, port,
 authentication).  If those look correct then try making a telnet 
connection.  To do this use Start | Run or open a 
command window and enter "telnet smtp.talktalk.net 25" (or whatever port
 TalkTalk uses for SMTP).  If you can 
make the connection then something is blocking Pegasus or there is a configuration issue in Pegasus.  
If not then there is a problem accessing smtp.talktalk.net.  
 
        <p>There are several thread on this forum on the topic that indicate causes including the port being blocked, possibly by a 
firewall/AV product (Comodo did this to me years ago after an update 
installed a new "feature"), a change by TalkTalk in port or authentication, a configuration issue in the SMTP host configuration in Pegasus 
Mail.</p>First verify that the SMTP host configuration in Pegasus 
matches the current TalkTalk SMTP connection requirements (server, port,
 authentication).&nbsp; If those look correct then try making a telnet 
connection.&nbsp; To do this use Start | Run or open a 
command window and enter "telnet smtp.talktalk.net 25" (or whatever port
 TalkTalk uses for SMTP).&nbsp; If you can 
make the connection then something is blocking Pegasus or there is a configuration issue in Pegasus.&nbsp; 
If not then there is a problem accessing smtp.talktalk.net.&nbsp;